Genetic Variations Are Linked to Alzheimer’s But Do Not ...

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July 20, 2010

Scientists have long known that certain forms of Alzheimer’s disease that occur at a young age are linked to specific defective genes that run in families. But less is known about the genes that cause the far more common late-onset form of Alzheimer’s that arises after age 65. While having a parent with the disease increases risk and certain genes may confer susceptibility to Alzheimer’s, specific gene markers cannot determine who will get the disease.

Now, a large study from The Netherlands found two new areas in the human genome that are associated with the late-onset form of Alzheimer’s. While having these genetic variations appeared to be linked to Alzheimer’s, they cannot be used to predict whether someone will actually develop the disease, the researchers found. The findings appeared in The Journal of the American Medical Association.

Other genes have been linked to late-onset Alzheimer’s. These include the APOE-E4 gene that increases someone’s risk of Alzheimer’s, but having the gene by no means guarantees you will get the disease. Other specific genes have also been linked to an increased Alzheimer’s risk.

The new study looked at the complete genomes of more than 35,000 men and women; about a quarter of them had Alzheimer’s disease. The researchers, from University Medical Center Rotterdam, found two new genetic areas – one on chromosome 2, and the other on chromosome 19 – that were linked to Alzheimer’s. The genes are not thought to be related to the APOE-E4 gene.

“One of every five persons aged 65 years is predicted to develop Alzheimer’s disease in their lifetime, and genetic variants may play an important part in the development of the disease,” the authors wrote. “The value of these associations may lie in the insights they could provide for research into the pathophysiological mechanisms of Alzheimer’s disease.”

In an accompanying editorial, Nancy L. Pedersen, Ph.D., of the Karolinska Institutet in Stockholm wrote that the findings of this study are a reminder that family history is very important, even for late-onset Alzheimer’s.

“The world is facing an escalation in Alzheimer’s prevalence now that life expectancy is well past 75 years in most developed countries,” Dr. Pedersen wrote. “Greater portions of the adult population will recognize signs of failing memory and cognitive impairment among their parents who are now among the oldest old.”

Dr. Pederson notes that population studies have shown that various lifestyle changes in midlife can help to decrease the risk of Alzheimer’s disease in old age or delay its onset. These include factors that keep the heart healthy, like exercise and a healthy diet.

Furthermore, she notes, extensive gene studies like these show that genetic profiling cannot be used to determine who will get Alzheimer’s disease. Continued study will help researchers to better understand why Alzheimer’s develops and may one day lead to a cure.

By ALZinfo.org, the Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Source:

Sudha Seshadri; Annette L. Fitzpatrick; M. Arfan Ikram; et al: Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease. Journal of the American Medical Association. Vol 303 (No. 18) May 2010; pages 1832-1840.

Nancy L. Pedersen: Reaching the Limits of Genome-wide Significance in Alzheimer Disease: Back to the Environment (editorial). Journal of the American Medical Association, Vol 303 (No. 18), May 2010, pages 1864-1865.

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